Project Summary/Abstract Given that depression is among the leading causes of impairment, a better understanding of the mechanisms that confer risk for its development is crucial. Although existing depression research has evaluated psychological and biological risk factors, much work has studied these factors in isolation. Further, few studies account for potential differential associations between risk factors and specific symptoms, which is possible due to advances in network modeling. This proposal seeks to integrate several risk factors into a multimodal model of depression etiology, utilizing a multi-method design to evaluate reward sensitivity and rumination as predictors of inflammatory reactivity to a reward-salient stress task and depressive symptoms. The project is designed to 1) evaluate the interplay between reward sensitivity and rumination in predicting inflammatory stress reactivity and depressive symptoms, 2) test whether inflammatory stress reactivity accounts for a significant indirect effect between both i) reward sensitivity and ii) rumination and later depressive symptoms, and 3) explore how reward sensitivity and rumination predict discrete symptoms and inflammatory biomarkers (and vice-versa) using network modeling. Given that emerging adults are at risk for both first onset and recurrence of depressive episodes, participants (Ps) in the study will be undergraduate students recruited from an ongoing online screener. Ps have completed measures of trait reward sensitivity, trait rumination, and baseline symptoms. Ps will be over-sampled for high and low reward sensitivity from the previous semester's respondents to increase the likelihood of extreme responses to the reward-salient stress task and risk for depressive symptoms. Selected Ps will complete a medical phone screener. Ps without a history of autoimmune disease will be recruited for a study visit in which they complete the medical screener again, a reward-salient stress task, a measure of post-task state rumination, and a diagnostic interview. Blood will be taken pre- and post-stressor to be assayed for inflammatory biomarkers. Ps will complete follow-up measures of depressive symptoms, trait reward sensitivity, and trait rumination one-week post-visit. Consistent with the NIMH Strategic Objectives and NIMH Research Domain Criteria, this multi-method study proposes to identify the interplay between risk mechanisms and pathophysiological processes to inform prevention and intervention (Strategic Objective 3) and to define mechanisms of complex behaviors transdiagnostically (Strategic Objective 1) with network analysis, using multiple units of analysis (physiology, self-report, behavior) to evaluate vulnerability to stress reactivity and depressive symptoms at both ends of the reward sensitivity dimension. A training plan has been designed that includes formal classwork, workshops, experiential learning, and mentorship in the etiology of depression, stress, network analysis, neurobiology, and psychoneuroimmunology. The study will occur in Temple University's clinical psychology program, which has a track record of conducting innovative, impactful NIH-funded research and training a future generation of researchers.